Solvent-free transesterification in a ball-mill over alumina surface

Article abstract of DOI:10.1016/j.tetlet.2012.05.127

An efficient procedure for transesterification has been developed in a ball-mill in the absence of any solvent, acid/base or metal catalyst. A variety of methyl, ethyl, allyl esters have been transesterified to higher benzyl and other esters in high yields by this procedure.

Full text of DOI:10.1016/j.tetlet.2012.05.127

Tetrahedron Letters 53 (2012) 4142–4144
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Solvent-free transesterification in a ball-mill over alumina surface
⇑
Tanmay Chatterjee, Debasree Saha, Brindaban C. Ranu
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient procedure for transesterification has been developed in a ball-mill in the absence of any sol-
vent, acid/base or metal catalyst. A variety of methyl, ethyl, allyl esters have been transesterified to higher
benzyl and other esters in high yields by this procedure.
Received 21 April 2012
Revised 26 May 2012
Accepted 27 May 2012
Available online 31 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Transesterification
Ball-milling
Alumina
Solvent-free
Green procedure
Transesterification is a useful reaction which has wide applica-
tions in academic as well as industrial research. Usually, methyl
and ethyl esters are readily available and thus they can be used
in transesterification for an easy access to higher homologues
which are of much importance for certain applications. Thus, a
number of procedures have been developed for this useful reac-
tion. Traditionally, a carboxylic ester was transesterified by reac-
tion with an alcohol in the presence of a protic and Lewis base or
acid.1,2 However, these procedures have limited scope due to their
incompatibility with sensitive functional groups and molecules.
Several milder reactions using organometallic catalysts,3 N-hetero-
cyclic carbene4 and indium triiodide5 among others6 have been
developed in recent times. These methods also have drawbacks
involving costly reagents and longer reaction times.
Reaction for a longer period than 2 h did not give a better result
(Table 1, entry 3). Acidic alumina alone (Table 1, entry 4) failed
to initiate any reaction although Al2O3–KF (Table 1, entry 5) im-
proved the yield marginally (30%). Silica gel (60–120 mesh) (Table
1, entry 6) was also not effective for this reaction.
In a typical experimental procedure13 a mixture of alcohol and
ester (little excess) absorbed in basic alumina was subjected to
ball-milling at 600 rpm for 2–3 h as required for maximum
Basic Al2O3
600 rpm, 6 balls,
ball-milling
O
O
R2
R3
R3 OH
R1
O
R1
O
+
Scheme 1. Transesterification in a ball-mill
Recently, ball-milling (mechanical grinding) has emerged as a
powerful tool for effecting a chemical reaction in a greener way.7
A variety of reactions such as homocoupling of terminal alkynes,8
Sonogashira,9 Michael10 and aldol reactions11 among others12 have
been performed very efficiently by this technique. As a part of our
continuing activities on green synthetic protocols, we report here
an efficient transesterification over an alumina surface by ball mill-
ing without requirement of any solvent and conventional catalyst
(Scheme 1).
Table 1
Standardization of reaction conditions in ball mill
O
Grinding
O
HO
O
auxiliary,
+
t/h
O
To standardize the reaction conditions several experiments for a
representative reaction of allyl acetate and benzyl alcohol were
carried out in a ball mill with the variation of grinding auxiliary
and reaction time. The results are summarized in Table 1. The reac-
tion over basic alumina gave best yield in 2 h (Table 1, entry 2).
Entry
Grinding auxiliary
t/h
Yield (%)
1
2
3
4
5
6
Basic Al2O3
Basic Al2O3
Basic Al2O3
Acidic Al2O3
KF–Al2O3
Silica
1
2
3
2
2
2
61
76
76
0
30
0
⇑
Corresponding author. Tel.: +91 33 24734971; fax: +91 33 24732805.
E-mail address: ocbcr@iacs.res.in (B.C. Ranu).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.127

T. Chatterjee et al. / Tetrahedron Letters 53 (2012) 4142–4144
4143
Table 2
conditions are mild and thus several functional groups and sensi-
tive heterocyclic units like thiophene, pyridine and furan remained
unaffected in this procedure. No solvent was used in the reaction
and the work-up procedure was skipped. Thus, use of organic sol-
vent was considerably reduced. Ball-milling accelerated the pro-
cess substantially and the reactions are complete by 2–3 h.
In conclusion, we have developed a simple and efficient proce-
dure for transesterification over alumina surface in ball-milling.
The notable advantages offered by this procedure are use of no sol-
vent and no acid or base catalyst in the reaction, considerably fast
reaction, tolerance to sensitive functionalities and molecules,
applicability to varied esters and alcohols and greener aspects
using less organic solvents and recyclability of grinding auxiliary.
To the best of our knowledge we are not aware of any earlier report
of transesterification under ball-milling using only a grinding aux-
iliary (alumina). We believe, this will make an important addition
to the existing procedures of transesterification and will find useful
applications in organic synthesis.
Transesterification of esters with alcohols
Basic Al2O3
O
O
600 rpm, 6 balls,
ball-milling
R2
R3
R3 OH
R1
O
R1
O
+
Entry R1
R2
R3
Time (h) Yielda (%) Ref.
1
2
3
4
5
6
7
8
Me
Me
Et
Me
n-pr
Ph
Vinyl Me
n-pr Me
Vinyl Me
Me
n-pr
Me
Et
Me
n-pr
Et
n-pr
Me
n-pr
Allyl
Allyl
Et
Allyl
Me
Ph-CH2–
2
2
2
2
2
3
76
75
71
70
81
80
78
72
70
76
71
73
76
75
70
72
75
72
70
4a
14
(3-Cl)C6H4-CH2–
(3-Cl)C6H4-CH2–
(4-F)C6H4-CH2–
(4-OCH3)C6H4-CH2–
15
16
17
Benzyl (4-OCH3)C6H4-CH2–
(4-OCH3)C6H4-CH2– 2.5
(4-NO2)C6H4-CH2–
(4-NO2)C6H4-CH2–
Ph-(CH2)2–
Ph-(CH2)2–
Ph-(CH2)3–
Ph-(CH2)3–
Ph-(CH2)4–
Ph-(CH2)4–
Ph-(CH2)5–
2
2.5
2
2
2
2
2
2
2
18
19
3b
20
4b
21
4b
22
9
10
11
12
13
14
15
16
17
18
19
Allyl
Me
Allyl
Et
Allyl
Me
Et
Me
Allyl
Me
Acknowledgments
Ph-(CH2)5–
CH3CH(Ph)(CH2)2–
CH3CH(Ph)(CH2)2–
2
2
2
23
We are pleased to acknowledge the financial support from CSIR,
New Delhi (Grant no. 01(2365)/10/EMR-II) for this investigation. T.
C. and D. S. also thank CSIR for their fellowships.
20
n-pr
Me
3
66
CH2
S
Supplementary data
21
Et
Et
2.5
71
24
N
O
C
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.05.127.
H2
22
n-pr
Me
2.5
65
C
H2
References and notes
23
24
Et
Et
2
2
76
69
3c
3c
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Reaction and Applications; Wiley-VCH: Weinheim, Germany, 2003.
2. (a) Fujita, T.; Tanaka, M.; Norimine, Y.; Shemune, H. J. Org. Chem. 1997, 62,
3824; (b) Shapiro, G.; Marzi, M. J. Org. Chem. 1997, 62, 7096; (c) Stanton, M. G.;
Gagne, M. R. J. Org. Chem. 1997, 62, 8240.
n-pr
Me
3. (a) Magens, S.; Plietker, B. J. Org. Chem. 2010, 75, 3715; (b) Magens, S.; Ertelt,
M.; Jatsch, A.; Plietker, B. Org. Lett. 2008, 10, 53. and references cited therein; (c)
Mino, T.; Hasegawa, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. J. Orgmet. Chem.
2007, 692, 4389.
4. (a) Grasa, G. A.; Guveli, T.; Singu, R.; Nolan, S. P. J. Org. Chem. 2003, 68, 2812; (b)
Zeng, T.; Song, G.; Li, C. J. Chem. Commun. 2009, 6249.
5. Ranu, B. C.; Dutta, P.; Sarkar, A. J. Org. Chem. 1998, 63, 6027.
6. (a) Otera, J. Acc. Chem. Res. 2004, 37, 288; (b) Yan, X.; Xueqiang, Z. Chin. J. Chem.
2011, 29, 1143.
7. (a) Stolle, A.; Szuppa, T.; Leonhardt, S. E. S.; Ondruschka, B. Chem. Soc. Rev. 2001,
40, 2317; (b) Rodriguez, B.; Bruckmann, A.; Rantanen, T.; Bolm, C. Adv. Synth.
Catal. 2007, 349, 2213.
8. Schmidt, R.; Thorwirth, R.; Szuppa, T.; Stolle, A.; Ondruschka, B.; Hopf, H. Chem.
Eur. J. 2011, 17, 8129.
9. Thorwirth, R.; Stolle, A.; Ondruschka, B. Green. Chem. 2010, 12, 985.
10. Wang, Y. F.; Chen, R. X.; Wang, K.; Zhang, B. B.; Li, Z. B.; Xu, D. Q. Green Chem.
http://dx.doi.org/10.1039/C2gC16521.
25
26
Ph
Et
Benzyl
Et
3
2
68
74
3c
25
(CH2)5
Me
CH
(CH2)5
27
Me
Allyl
2.5
67
26
27
Me
28
29
Et
Et
Et
Et
2.5
3
66
0
a
Yields refer to those of purified isolated products characterized by spectroscopic
11. Hernandez, J. G.; Juaristi, E. Tetrahedron 2011, 67, 6953.
data (IR, 1H NMR and 13C NMR).
12. (a) Thorwirth, R.; Stolle, A. Synlett 2011, 2200; (b) Tullberg, E.; Peters, D.; Frejd,
T. J. Orgmet. Chem. 2004, 689, 3778; (c) Szuppa, T.; Stolle, A.; Ondruschka, B.;
Hopfe, W. Green Chem. 2010, 12, 1288; (d) Thorwirth, R.; Bernhardt, F.; Stolle,
A.; Ondruschka, B.; Asghari, J. Chem. Eur. J. 2010, 16, 13236.
13. Representative experimental procedure for transesterification of allyl acetate
and benzyl alcohol (Table 2, entry 1). A mixture of allyl acetate (120 mg,
1.2 mmol) and benzyl alcohol (108 mg, 1 mmol) adsorbed on basic Al2O3
(3.5 g) was ball-milled in a 25 mL stainless steel vessel at 600 rpm using six
balls (d = 10 mm) for 2 h (PM 100, Retsch GmbH, Germany). The crude reaction
mixture was filtered through a short column of neutral alumina (hexane/
ether = 95:5) to provide benzyl acetate as a colourless liquid (114 mg, 76%), IR
conversion (TLC/NMR). A quick column chromatography of the
crude reaction mass over alumina (hexane/ether = 95:5) provided
pure product.
A wide range of carboxylic esters underwent transesterification
with several structurally diverse alcohols by this procedure. The
results are reported in Table 2. A variety of alcohols including
substituted benzyl, cinnamyl, heterocyclic, open chain and cyclic
secondary underwent exchange with methyl, ethyl, allyl and ben-
zyl esters to produce the corresponding transesters. The tertiary
alcohols did not participate in this transesterification process. In
general, the reactions are very clean and the products are obtained
in high purity. The yields of transesterified products are reasonably
good considering the reversible nature of the reaction. The reaction
3066, 3034, 2954, 1740, 1488, 1026 cmÀ1 1H NMR (300 MHz, CDCl3) d 7.36 (s,
;
5H), 5.12 (s, 2H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3) d 171, 136.0, 128.6
(2C), 128.3 (3C), 66.3, 21.0. These data are in good agreement with those of an
authentic sample.
This procedure is followed for all the reactions listed in Table 2. The known
products were identified by comparison of their spectroscopic (IR, 1H NMR and
13C NMR) data with those reported (See references in Table 2). The unknown
products (Table 2, entries 3, 7, 16, 17, 19, 20 and 22) were properly
characterized by their spectroscopic (IR, 1H NMR and 13C NMR) data which
are provided below.

4144
T. Chatterjee et al. / Tetrahedron Letters 53 (2012) 4142–4144
3-Chlorobenzyl propionate (Table 2, entry 3): Colourless liquid; IR 3470, 3066,
2982, 2943, 2831, 1741, 1600, 1577, 1462, 1431, 1377, 1346, 1273, 1176, 1080,
(Thiophen-2-yl) methyl butyrate (Table 2, entry 20): Colourless liquid; IR 2962,
2856, 1735, 1440, 1365, 1226, 1168, 1070, 966, 854, 831, 702 cmÀ1 1H NMR
(500 MHz, CDCl3) d 6.99–6.97 (m, 3H), 5.27 (s, 2H), 2.32 (t, J = 7.5 Hz, 2H), 1.70–
1.64 (m, 2H), 0.94 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 173.5, 140.7,
128.1, 126.8, 126.1, 65.9, 36.2, 18.5, 13.7; anal calcd for C9H12O2S: C 58.67, H
6.56%; Found: C 58.74, H 6.62%.
;
871, 783 cmÀ1
;
1H NMR (300 MHz, CDCl3) d 7.34–7.21 (m, 4H), 5.08 (s, 2H),
2.43–2.35 (m, 2H) 1.17 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 174.2,
140.3, 134.5, 129.9, 128.2, 128.1, 126.2, 65.3, 27.6, 9.2; Anal. calcd for
C
10H11ClO2: C 60.46, H 5.58%; Found: C 60.32, H 5.66%.
4-Methoxybenzyl acrylate (Table 2, entry 7): Colourless liquid; IR 2956, 2837,
1722, 1614, 1516, 1464, 1406, 1296, 1249, 1172, 1035, 985, 966, 810 cmÀ1 1H
(Furan-2-yl) methyl butyrate (Table 2, entry 22): Colourless liquid; IR 2964,
;
2931, 2875, 1735, 1512, 1458, 1381, 1249, 1170, 1080, 970, 744 cmÀ1 1H NMR
;
NMR (300 MHz, CDCl3) d 7.31 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 6.42 (d,
J = 17.4 Hz, 1H), 6.19–6.09 (m, 1H), 5.82 (d, J = 10.2 Hz, 1H), 5.13 (s, 2H), 3.80 (s,
3H); 13C NMR (75 MHz, CDCl3) d 166.1, 159.7, 130.9, 130.1 (2C), 128.5, 128.0,
114.0 (2C), 66.2, 55.2; Anal. calcd for C11H12O3: C 68.74, H 6.29%; Found: C
68.88, H 6.19%.
(500 MHz, CDCl3) d 7.34 (s, 1H), 6.33–6.28 (m, 2H), 4.99 (s, 2H), 2.24 (t, J = 7 Hz,
2H), 1.62–1.55 (m, 2H), 0.863 (t, J = 7 Hz, 3H); 13C NMR (125 MHz, CDCl3) d
173.4, 149.8, 143.8, 110.7, 110.6, 58.0, 36.1, 18.5, 13.7; Anal. calcd for C9H12O3:
C 64.27, H 7.19%; Found: C 64.34, H 7.11%.
14. Karimi, B.; Maleki, J. J. Org. Chem. 2003, 68, 4951.
5-Phenylpentyl propionate (Table 2, entry 16): Colourless liquid; IR 2937,
2858, 1737, 1602, 1496, 1454, 1350, 1190, 1084,
15. Kadam, S. T.; Kim, S. S. Synthesis 2008, 20, 3307.
16. Bamoharram, F. F.; Heravi, M. M.; Roshani, M.; Jahangir, M.; Gharib, A. Appl.
Catal. A: General 2006, 302, 42.
746, 700 cmÀ1 1H NMR (500 MHz, CDCl3) d 7.28–7.24 (m, 2H), 7.18–7.15 (m,
;
3H), 4.05 (t, J = 7 Hz, 2H), 2.61 (t, J = 7.5 Hz, 2H),
17. Iranpoor, N.; Firouzabadi, H.; Khalili, D. Org. Biomol. Chem. 2010, 8, 4436.
18. Akceylan, E.; Yilmaz, M. Tetrahedron 2011, 67, 6240.
19. Merski, M.; Townsend, C. A. J. Am. Chem. Soc. 2007, 129, 15750.
20. Bartoli, G.; Bosco, M.; Dalpozzo, R.; Marcantoni, E.; Massaccesi, M.; Sambri, L.
Eur. J. Org. Chem. 2003, 4611.
2.32–2.28 (m, 2H), 1.67–1.61 (m, 4H), 1.42–1.35 (m, 2H), 1.12 (t, J = 7.5 Hz,
3H); 13C NMR (125 MHz, CDCl3) d 174.7, 142.5, 128.5 (2C), 128.4 (2C), 125.8,
64.4, 35.9, 31.1, 28.6, 27.7, 25.7, 9.3; HRMS calcd for C14H20O2Na [M+Na]+:
243.1361; Found: 243.1362.
5-Phenylpentyl butyrate (Table 2, entry 17): Colourless liquid; IR 2935, 2858,
21. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1995, 117,
4413.
1732, 1602, 1494, 1454, 1257, 1184, 1091, 910, 758, 698 cmÀ1 1H NMR
;
(300 MHz, CDCl3) d 7.25 (d, J = 7 Hz, 2H), 7.18–7.14 (m, 3H), 4.05 (t, J = 7 Hz,
2H), 2.61 (t, J = 7.5 Hz,
2H), 2.25 (t, J = 7.5 Hz, 2H), 1.71–1.59 (m, 6H), 1.43–1.35 (m, 2H), 0.93 (t,
J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 173.8, 142.4, 128.4 (2C), 128.3 (2C),
125.7, 64.2, 36.3, 35.8, 31.1, 28.6, 25.6, 18.5, 13.7; HRMS calcd for C15H22O2Na
[M+Na]+: 257.1517; Found: 257.1518.
22. Purohit, A.; Radeke, H.; Azure, M.; Hanson, K.; Benetti, R.; Su, F.; Yalamanchili,
P.; Yu, M.; Hayes, M.; Guaraldi, M.; Kagan, M.; Robinson, S.; Casebier, D. J. Med.
Chem. 2008, 51, 2954.
23. Kaukoranta, P.; Engman, M.; Hedberg, C.; Bergquist, J.; Anderssona, P. G. Adv.
Synth. Catal. 2008, 350, 1168.
24. Yokota, K.; Tatamidani, H.; Fukumoto, Y.; Chatani, N. Org. Lett. 2003, 5, 23.
25. Kumar, P.; Pandey, R. K.; Bodas, M. S.; Dongareb, M. K. Synlett 2001, 206.
26. Chen, M. S.; Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005,
127, 6970.
3-Phenylbutyl butyrate (Table 2, entry 19): Colourless liquid; IR 2962, 2875,
1735, 1602, 1492, 1454, 1359, 1305, 1253, 1178, 1091, 761, 700 cmÀ1 1H NMR
;
(500 MHz, CDCl3) d 7.29 (t, J = 7 Hz, 2H), 7.20–7.17 (m, 3H), 4.04–3.92 (m, 2H),
2.86–2.81 (m, 1H), 2.24 (t, J = 7.5 Hz, 2H), 1.93–1.89 (m, 2H), 1.67–1.60 (m, 2H),
1.28 (d, J = 7 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 173.8,
146.4, 128.6 (2C), 127.0 (2C), 126.3, 62.8, 37.0, 36.8, 36.3, 22.3, 18.6, 13.8;
HRMS calcd for C15H20O2Na [M+Na]+: 243.1361; Found: 243.1361.
27. Ranu, B. C.; Dey, S. S.; Hazra, A. Green Chem. 2003, 5, 6027.